Drug Discovery@nature.com 3 August 2012

TABLE OF CONTENTS 3 August 2012 News Analysis Research Highlights Research & Reviews Careers Nature Reviews Drug Discovery is on Twitter Advertisement Nature Communications #4 in multidisciplinary sciences with first Impact Factor Nature Communications has joined Nature at the top of the multidisciplinary sciences category with its first impact factor of 7.396* Launched in April 2010, Nature Communications is a multidisciplinary online-only journal publishing high quality research across the natural sciences. *2011 Journal Citation Reports® (Thomson Reuters, 2012)   News Top Overtaking the DILI Model-T doi:10.1038/nrd3818 A new €32 million project aimed at understanding drug-induced liver injury is the latest of several collaborative efforts that could help drug firms better test for candidate-killing toxicity signals. Full Text PDUFA V goes back to basics doi:10.1038/nrd3819 20 years after the first PDUFA provided the FDA with additional resources, regulators and industry are refocusing on review times and approval rates. Full Text Deal watch: Roche deal targets glutamate in neurodevelopmental disorders doi:10.1038/nrd3808 Roche and Seaside Therapeutics will collaborate on antagonists of metabotropic glutamate receptor 5 and agonists of γ-aminobutyric acid type B receptors, aiming to treat both autism spectrum disorders and Fragile X syndrome. Full Text Trial watch: Novel antimicrobial fights TB resistance doi:10.1038/nrd3809 Otsuka Pharmaceutical's delamanid has demonstrated activity in patients with multidrug-resistant tuberculosis in a Phase II trial. Full Text Analysis Top Taming T cells in T1D doi:10.1038/scibx.2012.746 Separate teams have evidence that blocking Il-7 signaling in mice can arrest the autoimmune activity behind type 1 diabetes. Whether the findings will translate to the clinic depends on whether the cytokine has the same effect in mice and humans. Full Text Fresh from the pipeline: Pasireotide doi:10.1038/nrd3788 In April 2012, pasireotide was granted European marketing authorization for the treatment of Cushing's disease, providing a new option for patients for whom surgery has failed. Full Text From the analyst's couch: A new dawn in the sleep disorders pipeline? doi:10.1038/nrd3789 This analysis article looks at the growing interest in novel molecular targets for sleep disorders, and the market opportunities in this area of significant unmet need. Full Text Research Highlights Top Cancer: PD1 makes waves in anticancer immunotherapy doi:10.1038/nrd3806 Two papers describe early-stage clinical trials of two monoclonal antibodies that target signalling through the T cell co-inhibitory receptor programmed cell death protein 1, suggesting that such antibodies might provide a new benchmark for anticancer immunotherapy. Full Text Metabolic disorders: New target for appetite control doi:10.1038/nrd3803 The G protein-coupled receptor GPR17 has been identified as a direct target of the forkhead box protein O1 transcription factor, which activates AGRP-expressing neurons to regulate food intake in mice. Full Text Neurodegenerative disorders: Reversing Huntington's disease doi:10.1038/nrd3804 New research shows that transient infusion of single-stranded antisense oligonucleotides in a mouse model results in sustained improvements in motor function and behaviour. Full Text Research & Reviews Top Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases doi:10.1038/nrd3800 This review looks at current and future drugs that may be available to treat a broad range of inflammation-related conditions by blocking interleukin-1. Full Text G protein-coupled receptors for energy metabolites as new therapeutic targets doi:10.1038/nrd3777 This review summarizes the functions of several recently discovered metabolite-sensing GPCRs and discusses the emerging pharmacological agents being developed to target these for metabolic disorders. Full Text A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response doi:10.1038/nature11262 A paper in Nature provides encouragement for designing small-molecule inhibitors to allow selective pharmacological intervention across the JMJ family. Full Text MDM4 is a key therapeutic target in cutaneous melanoma doi:10.1038/nm.2863 A paper in Nature Medicine identifies MDM4 as a key determinant of impaired p53 function in human melanoma and designates MDM4 as a promising target for antimelanoma combination therapy. Full Text Drug Discovery JOBS of the week Senior Research Technician in Drug Discovery University of Dundee Postdoctoral Research Associate - Drug Metabolism and Pharmacokinetics Scripps Fl In Vivo Biologist-Biopharmaceutical Drug Discovery Eli Lilly Principal Investigator positions in Biological Chemistry & Drug Discovery University of Dundee, College of Life Sciences Postdoctoral Researcher Marine Natural Products in Drug Discovery NUI Galway Ireland More Science jobs from Drug Discovery EVENT ADME, PK/TK, and Drug Metabolism in Drug Discovery and Development 17.-19.09.12 Dublin, Ireland More science events from Careers Top Career snapshots archive Career snapshots feature people associated with drug discovery and drug development, with the aim of providing expert insights and advice on a wide range of positions and career paths in this field. 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